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A Case of Brucellosis Associated with Histiocytic Necrotizing Lymphadenitis: a Diagnostic Pitfall

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A Case of Brucellosis Associated with Histiocytic Necrotizing Lymphadenitis: a Diagnostic Pitfall J Interdiscipl Histopathol 2013; 1(5): 274-279 ISSN: 2146-8362 Case Report A Case of Brucellosis Associated With Histiocytic Necrotizing Lymphadenitis: A Diagnostic Pitfall Nicole Dalton Wheeler1, Marian Rollins-Raval2,3, Steven H. Swerdlow3, Swati Modi4, Kimberly Liang4, Robyn T. Domsic4, and Kathleen R. Sheridan1 1Department of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA 2Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA 3Division of Hematopathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA 4Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA Received: June 26, 2013 Abstract Accepted: July 22, 2013 Human cases of brucellosis are rare in the United States and difficult to diagnose. We report a case of a young female who underwent a diagnostic investigation of Published Online: July 24, 2013 fever of unknown origin, which included a lymph node biopsy. The biopsy was DOI: 10.5455/jihp.20130722113848 consistent with Kikuchi’s Disease, or histiocytic necrotizing lymphadenitis, an entity where the major differential diagnosis is systemic lupus erythematosus. Corresponding Authors: Interestingly, serologic studies supported the diagnosis of brucellosis. Brucellosis Nicole Dalton Wheeler, MD has rarely been associated with histiocytic necrotizing lymphadenitis. This Kathleen Sheridan, MD association has never been reported in the United States, thus suggesting that Department of Infectious Diseases, University of Pittsburgh Medical Center, brucellosis should be considered in the differential for histiocytic necrotizing 3601 Fifth Avenue, 3rd floor Falk Medical lymphadenitis, along with lupus-like autoimmune disease. As the prognosis and Building, Suite 3A, Pittsburgh, PA 15213, treatment of histiocytic necrotizing lymphadenitis, brucellosis, and systemic lupus USA erythematosus are distinct, it is important to differentiate these entities. [email protected] [email protected] Keywords: Brucellosis; Kikuchi’s disease; histiocytic necrotizing lymphadenitis; systemic lupus erythematosus © 2013 GESDAV INTRODUCTION focal complication is osteoarticular involvement, such as reactive arthritis, sacroiliitis, or spondylitis [2]. Human brucellosis, though rare in the U.S. with only 100 cases per year reported [1], is the most common When there is a high index of suspicion, diagnosis is zoonosis in the world [2]. Humans can acquire the best made by culture of the organism from blood, or disease by: ingestion of raw dairy products or infected bone marrow, though poorly sensitive. A rise in meat; by contact with secretions or blood of antibody titers is suggestive of disease, but falsely chronically-infected animals; or by inhalation of positive results are possible. A positive serum contaminated aerosols. The incubation period is usually agglutination test may be more specific [4]. A lymph two to four weeks, followed by an onset that can be node biopsy is not a routine part of the diagnostic acute or insidious [3]. The most common clinical work-up, and the histologic findings are not well manifestations of acute brucellosis are non-specific, described in the literature. and include intermittent fevers, arthralgias, and fatigue. We report a case of fever of unknown origin in which However, the spectrum of disease includes serologic studies supported a diagnosis of brucellosis asymptomatic to exhibiting diverse signs and and lymph node biopsy showed histology consistent symptoms related to almost any organ system [4]. with histiocytic necrotizing lymphadenitis, which has Endocarditis is a relatively rare complication (<2%), rarely been associated with brucellosis. but accounts for the most deaths [3]. The most common 274 Wheeler et al. CASE PRESENTATION plasma cells and histiocytes. The necrotic areas showed mostly necrotic cellular debris with admixed An active, otherwise healthy, 22-year-old female was lymphocytes and histiocytes, including occasional admitted for further work-up of fever of unknown histiocytes with crescentic nuclei (Figure 1B). origin. She has a past medical history of acne, treated Particularly the edge of the necrotic areas showed a with doxycycline 50mg daily. She lives in central focally prominent population that appeared to represent Pennsylvania, with no history of international travel. plasmacytoid dendritic cells (Figure 1C). Paraffin She was working in a laboratory that studies New section immunohistochemical stains demonstrated B- Zealand mud snails. Otherwise, she had no farm animal cells predominantly in follicles, as well as numerous T- contact and did not ingest any unpasteurized milk or cells mostly outside of the follicles. There were cheese. There was no family history of autoimmunity prominent aggregates of CD123 positive plasmacytoid or immunodeficiency. dendritic cells, particularly at the periphery of the Approximately two months prior to her presentation, necrotic regions (Figure 1D). There were numerous she developed fevers, fatigue, malaise, myalgias, right CD4 positive cells, outside of the necrotic areas, but upper quadrant pain and weight loss. Given her fevers fewer CD4 positive lymphocytes within the necrotic and findings of a new pancytopenia, she was admitted areas (Figure 1E). In contrast, CD8 positivity was more to a local hospital. The work-up was largely prominent within the necrotic areas, highlighting some unremarkable, including: serology for hepatitis A/B/C, viable cells as well as debris (Figure 1F). The Epstein-Barr Virus (EBV), Cytomegalovirus, and numerous CD68 positive histiocytes, concentrated in Lyme disease; Tuberculin skin test; antistreptolysin O and around the necrotic areas, were also titer; and a transthoracic echocardiogram. Contrast- myeloperoxidase positive, but there were only rare enhanced CT of the abdomen and pelvis revealed myeloperoxidase positive neutrophils (Figures 1G-H). mesenteric lymphadenopathy. She was transferred to Immunohistochemical stains for cytomegalovirus our institution five days later for further management. (CMV), Bartonella henselae and herpes simplex virus 1 and 2 were negative. AFB and Grocott stains were On examination, she was febrile to 39.3 °C, but other negative for acid fast bacilli and fungal organisms, vital signs were within normal limits. She had tender respectively. There were no hematoxylin bodies or cervical lymphadenopathy. Her heart rate was irregular evidence of the Azzopardi phenomenon identified. with skipped beats, and without murmur. Upon examination of her abdomen, there was right upper quadrant tenderness and hepatomegaly, without Table 1: Select laboratory values of the patient obtained at rebound or guarding. Her musculoskeletal exam admission. revealed bilateral first and second metacarpophalangeal Patient value Reference range joints that were mildly full and tender to palpation, with WBC 1,000/L 3,800 – 10,600 a patch of overlying erythema, as well as tender ankles. The remainder of the physical examination was normal. Neutrophils 54% 44 - 77% On admission, the patient had pancytopenia and Bands 7% 0 - 5% elevated liver function tests, as well as a borderline Lymphocytes 31% 13 - 44% positive anti-histone antibody (Table 1). Her blood Monocytes 7% 4 - 13% chemistry panel was normal. Blood cultures drawn Atypical 1% 0% while already on antibiotics were negative. She had lymphocytes first degree atrioventricular block on admission EKG that progressed to second degree heart block on Hemoglobin 7.9 gm/dL 11.6 - 14.6 hospital day 5. Results of transthoracic Platelets 121,000/L 156,000 – 369,000 echocardiography and cardiac MRI showed no Creatinine 0.7 mg/dL 0.5 - 1.4 evidence of myocarditis or endocarditis. ALT 82 IU/L 14 - 54 She underwent cervical lymph node biopsy on hospital AST 126 IU/L 15 - 41 day 6 (Figure 1 A-H). Grossly, the left cervical lymph node biopsy showed areas of tan tissue juxtaposed with Bilirubin 0.6 mg/dL 0.3 - 1.5 areas of yellow and apparently hemorrhagic areas. The Alkaline 61 IU/L 38 - 126 histologic sections demonstrated a reactive-appearing Phosphatase lymph node with areas of extensive necrosis without HIV Antibody negative negative suppuration, but with abundant karyorrhexis and debris Anti-histone 1.2 U <1.0 (Figure 1A). The viable areas showed follicles and antibody otherwise a heterogeneous mixture of small lymphocytes, occasional transformed lymphocytes, 275 J Interdiscipl Histopathol 2013; 1(5): 274-279 Brucellosis associated with histiocytic necrotizing lymphadenitis Figure 1: Cervical lymph node biopsy. A: A low magnification image demonstrates a reactive lymph node with areas of extensive eosinophilic necrosis. B: The necrotic areas showed some lymphoid cells and histiocytes, including some with crescentic nuclei but note the absence of neutrophils. C: The following immunohistologic stains (D-H) demonstrates this region of the histologic section with the necrotic area at the top of the image. D: CD123 highlights moderately numerous plasmacytoid dendritic cells at the periphery of the necrotic area. E: There were many CD4 positive T-lymphocytes in the more viable lymph node with fewer in the necrotic area. Many histiocytes are also more weakly CD4 positive. F: In contrast, there were few CD8 positive cells in the more viable area with more numerous positive cells and debris in the necrotic area. G: The necrotic area also demonstrated moderately numerous CD68 positive
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